Several publications and patent documents are referenced in this application in order to more fully describe the state of the art to which this invention pertains. The disclosure of each of these publications and documents is incorporated by reference herein in its entirety.
SCZ is a severe neuropsychiatric illness with onset in late adolescence or early adulthood. Typified by distorted perceptions of reality (hallucinations and delusions), social deficits, disorganized language and behavior, and mild cognitive dysfunction, it is a devastating and relatively common disorder, affecting about 1% of worldwide populations. The prevailing theory is that SCZ results from anomalous neurodevelopment, either from a teratogenic fetal exposure or from defective genes. Cores of family, twin, and adoption studies have confirmed a major hereditary component for SCZ risk, yet no particular gene has been identified for the disorder. The present consensus is that SCZ is an etiologically heterogeneous syndrome, with multiple genes, various exposures, and gene-environment interactions producing a common phenotype. For many genetic diseases, the birth of an affected individual into an otherwise unaffected family (sporadic case) signals a possible de novo mutation. In contrast, sporadic cases of SCZ are usually presumed to originate from environmental factors that either act independently or through synergistic effects with underlying genes. See, e.g., Malaspina et al. (Am J Med Genetics (Neuropsychiatric Genetics) 2002, 114:299-303).